The following is a summary of our findings over the past year: Neural Induction (Normal) - appears to be long process continuing over several days of development; the early component (9.5 days) is necessary for continued development and the later component (10.5 days) directing orderly morphogenesis of labyrinthine form. Preliminary ultrastructure findings have not shown cell contacts between the brain stem and the developing otocyst. Neural Induction (Abnormal) - ultrastructural studies have revealed abnormal patterns of cell death in mutant (kr/kr) mouse otocysts in comparison to findings in comparable otocysts of their heterozygote littermates. The distance between the brain and otocyst was also much greater (4 to 10 times) in the mutant embryos when compared to heterozygotes or normal mouse embryos. Epithelio-Mesenchymal Tissue Interactions (Normal) - the results of microsurgical organ culture experiments and the use of proteolytic enzymes have shown that interactions occurring between the surrounding periotic mesenchyme tissues and the epithelium of the developing otocyst are important to the sequential expression of those genes which code for labyrinthine morphogenesis and differentiation of inner ear sensory structures. Intralabyrinthine Pressure - organ culture experiments designed to reduce intralabyrinthine pressure in developing inner ears did not show any differences in morphogenesis or differentiation of sensory structures between otocysts cannulated with a solid glass rod or those cannulated with a hollow glass tube. Congenital Malformation Model -ultrastructure of the "in vitro" development of sensory hair cells of homozygotic and heterozygotic kreisler inner ear explants is in progress.